The present invention relates to devices for delivering, dispensing or administering substances, and to methods of making and using such devices. It also relates to methods for delivering, dispensing or administering substances, and to establishing, implementing and using such methods. More particularly, it relates to a method and a device for calculating a bolus amount, including for continuous subcutaneous administration of insulin by means of an insulin pump, whereby rapid-acting insulin can be administered to, for example, provide a patient with a bolus amount of insulin for the consumption of carbohydrates.
Human beings should have a blood glucose level of approximately between 70 and 126 mg/dl; with the help of insulin, glucose in the blood can be used as fuel in the body's cells to provide the body with vital energy. Normally, the insulin required is generated by the pancreas, which produces the requisite amount of insulin and releases it into the body. Diabetics need to be supplied with insulin artificially. Insulin pumps that are intended to completely or at least partially replace the function of the malfunctioning pancreas are often used for this purpose. Small quantities of insulin are continuously infused into a patient's subcutaneous fatty tissue over the course of the day, usually in the abdominal region, by means of a catheter; a quantity of insulin which is delivered continuously to a patient over the course of the day and which depends on the time of day may be referred to as the basal rate. (Note that, as used herein, the term “basal rate” is intended to mean a rate of supply, including continuous supply, of a chemical, substance or process for producing a desired effect, including, for example, a rate of insulin supply for controlling cellular glucose and amino acid uptake.) The basal insulin requirement differs from patient to patient and is subject to circadian fluctuations, so an insulin pump is programmed with the basal-rate profile in a patient-specific manner. When food is consumed, a larger amount of insulin, a so-called bolus, is needed to enable the body's cells to make use of the quantity of carbohydrate or sugar consumed in the food.
Thus, whenever patients want to consume carbohydrates or correct an elevated blood-glucose level, they are obliged to administer bolus insulin. The bolus amount required for this should be calculated as accurately as possible. A possible way of calculating a recommendation for the amount of insulin to be delivered is to use the following formula, which may be referred to as formula 1:
                              Rec          ⁡                      [                          I              .              U              .                        ]                          =                ⁢                                                            x                carbohydrates                            ⁡                              [                g                ]                                      *                                          A                meal                            ⁡                              [                                                      I                    .                    U                    .                                    *                                      g                                          -                      1                                                                      ]                                              +                                                ⁢                  (                                                    x                BGactual                            ⁡                              [                                  mmol                  *                                      l                                          -                      1                                                                      ]                                      -                                          B                BGtarget                            ⁡                              [                                  mmol                  *                                      l                                          -                      1                                                                      ]                                      -                                                          ⁢                                            C                              insulin                ⁢                                                                  ⁢                still                ⁢                                                                  ⁢                effective                                      ⁡                          [                              I                .                U                .                            ]                                *                                                            ⁢                                    D              correction                        ⁡                          [                              mmol                *                                  l                                      -                    1                                                  *                                  I                  .                  U                  ⁢                                      .                                          -                      1                                                                                  ]                                )                *                                        ⁢                                            (                                                D                  correction                                ⁡                                  [                                      mmol                    *                                          l                                              -                        1                                                              *                                          I                      .                      U                      ⁢                                              .                                                  -                          1                                                                                                      ]                                            )                                      -              1                                .                    
In formula 1, the variable Rec [I.U.] refers to the recommended number of insulin units I.U. to be administered as a bolus, as calculated from the formula. To calculate the recommended number of insulin units to be delivered, two variable parameters are used, namely the parameter xcarbohydrates, which represents the amount, in grams, of carbohydrate consumed, or to be consumed, as food and the parameter xBG actual, which represents the measured or actual blood-glucose value in mmol/l. The following, preset parameters are also used: Ameal, which represents the amount of insulin units needed to process or compensate for one gram of carbohydrate, BBG target, which represents the target or nominal blood-glucose value in mmol/l, and Dcorrection, which indicates how the blood-glucose value is reduced by the effect of one unit of insulin in mmol/l per unit of insulin. The parameter Cinsulin still effective is used to take account of insulin that has already been injected or infused, it being possible to calculate this parameter on the basis of algorithms that can calculate the remaining activity of infused insulin in the body at a given time after infusion. The amount of insulin administered over a preceding period of e.g. 6 to 12 hours can be taken into account, for example.
If formula 1, as shown above, is used to calculate a bolus dose, constant values are preset for the parameters Ameal and Dcorrection over preset periods, depending on the time of day. For example, a value of 0.9 insulin units (I.U.) per bread unit (corresponding to 12 g of carbohydrate) is set for the parameter Ameal for the period between 22:00 h and 06:00 h. A value of 1.5 insulin units per bread unit is set for the period between 6:00 h in the morning and 10:00 h in the morning, a value of 1.0 insulin units per bread unit between 10:00 h and 16:00 h, and a value of 1.4 insulin units per bread unit between 16:00 h and 22:00 h. The parameter Dcorrection is assigned a constant value depending on the time of day in the same way, and, on the basis of these constants assigned to the parameters Ameal and Dcorrection, a recommended number of insulin units to be administered as a bolus is calculated using formula 1.
A method for calculating a bolus value on the basis of a varying daily prediction of the amount of insulin required is known from U.S. Pat. No. 6,691,043 B2.